Many species of protozoa are obligate intracellular parasites, including some, such as malaria, that are important agents of disease. Little is known as to why these eukaryotic cells can grow and reproduce only within another species of eukaryotic cell. Do they parasitize directly the energy-forming mechanisms of the host cell, or do they gain an energetic advantage by parasitizing the biosynthetic capabilities of the host cell? How are interactions with the host cell regulated? Extracellular maintenance of the parasites provides an approach toward answering these and other basic questions in the biology of parasitism. Only one kind of intracellular parasite has been kept alive and developing extracellularly. This is the bird malaria Plasmodium lophurae. The erythrocytic trophozoites of this organism, when removed from their host erythrocytes, will develop into schizonts in a medium of red cell extract. Exogenous ATP is a requirement for this development. We have now observed an initial extracellular development of merozoites of P. falciparum for which ATP and pyruvate are essential. We propose to investigate in detail this phenomenon both with regard to the constituents of the medium and to the fine structure of the developing merozoites. Special attention will be given to determining whether ATP can be replaced by ADP or AMP or by other nucleotides and to attempting to specify the role of the ATP. We will also investigate the possible effects of red cell membrane proteins on this initial extracellular development of falciparum merozoites. The information to be obtained will contribute specifically to knowledge of the physiology of the pathogenic erythrocytic stages of malaria parasites, with potential consequences for treatment and control of malaria. It will also bear on intracellular parasitism in general and on intracellular regulatory mechanisms.